Events honor early patients of novel Parkinson’s study

From left, Wayne Holt, Dale Nevels, Duane Cook and Bill Schmalfeldt are among the group of patients who volunteered for Vanderbilt’s study into using deep brain stimulation (DBS) to treat late-stage Parkinson’s disease.

Pioneers of Parkinson’s disease research are gathering at Vanderbilt University Medical Center today to celebrate the end of a study that was an important first step in the quest to find a way to slow the progression of the degenerative movement disorder.

In 1997, the FDA approved a treatment for late-stage Parkinson’s called deep brain stimulation (DBS). The therapy, manufactured by Medtronic, involves a thin wire implanted deep in the brain running to a small pulse generator implanted under the collarbone that emits an electrical current.

While DBS is an accepted therapy for patients not helped by medication, there is no treatment proven to slow the progression of Parkinson’s.

“There is the possibility that if deep brain stimulation is applied early, it can slow down the disease,” said David Charles, M.D., professor and vice-chair of Neurology and principal investigator of the study.

But before this theory could be tested, there needed to be an initial safety and tolerability study to ensure that giving early DBS would not cause unforeseen problems.

Beginning in 2006, 35 research subjects were recruited, given a thorough explanation of the risks, and randomized to receive DBS or be part of a standard of care control group.

The phase 1 clinical trial was the first and only of its kind in the world to test DBS in such an early stage of Parkinson’s disease.

“There were a lot of questions surrounding this study. Patients can expect five to seven good years on medication alone, so is it ethical to expose them to the risk associated with surgery when the group had only been on medicine an average of two years? One patient did have a mild stroke following surgery and is cognitively impaired. That’s where the rubber meets the road about people stepping up because the risks are real,” Charles said.

“Then there were questions about whether patients, since they had decided they wanted the surgery, would drop out if they were randomized to medicine. But only one patient dropped out.”

Charles said these 35 volunteers are a special group.

“I’ve gotten to know these people. They are a very spiritual group, and helping others was the resounding sentiment and at the core of why many wanted to join the study.”

For Janet Frazer, a first-grade teacher who retired to the mountains in Fairfield Glade, Tenn., it’s exciting to be in the first group of research subjects that could potentially lead to a cure.

“After reading so much about Parkinson’s, I decided I wanted to be involved in research. It’s so important to solving many of our medical problems. I feel very blessed in my life — I could easily have been diagnosed with something worse — and the least I could do was give back,” Frazer said.

Frazer was randomized to the standard of care group, which took the medications typically given to Parkinson’s patients.

Duane Cook, a lawyer from Georgetown, Ky., said the participants receiving standard of care like Frazer made the biggest sacrifice.

“I was interested in anything that would slow the progression,” he said. “I knew there was a risk in surgery, but that paled in comparison to the risk of early dementia. It would have been hard not to have the surgery. Those people are the real heroes.”

Cook, who opened his own law firm at 59 and is an avid golfer, said his disease has not progressed.

“I work at the keyboard every day and golf all the time. Most people wouldn’t look at me and say I’ve got Parkinson’s.”

In addition to agreeing to the risky surgery, study participants also committed to five weeklong stays at VUMC’s Clinical Research Center over a two-year period.

For Dale Nevels, a manufacturer’s representative in Memphis who received DBS, those visits were a glimpse of life without any treatment options.

“I’d call it hell week. The first day they stopped all [Parkinson’s] medications and turned off the neurostimulators. It took a few days to float to the bottom of the ocean, and they would do tests,” he said.

“Then I was plugged back in and floated back to the top. It was so psychologically and physically demanding. And I would always say, ‘thank goodness I have had the surgery.’”
Many of the participants keep in touch and even play golf regularly.

At the gathering today, they will learn the results of the study, which will be formally published in the winter, and hear presentations from French scientist Alim-Louis Benabid, who was the first to use DBS to treat movement disorders in 1987, and Caryl Sortwell, Ph.D., professor in the Division of Translational Science and Molecular Medicine at Michigan State University, who is conducting basic science research that may explain how early stimulation could be neuro-protective.

“It was a tough decision to join the study, and these volunteers gave a huge amount of time, so we feel an obligation to give back to them and share what we learned from them,” Charles said.

On Aug. 25, VUMC is leading a national consortium of more than 20 neurologists and neurosurgeons from academic medical centers around the country to discuss the next steps of researching DBS for early-stage Parkinson’s disease.

While the results are still pending on the safety and tolerability of the approach, planning has begun for the next stage of the study — a large, multi-national, multi-center trial.

“This is how new therapies come about — partnerships between universities, industry and patient volunteers,” Charles said. “The patients in this study deserve all the credit. They are truly heroes because they stepped up to accept potentially devastating consequences in hopes of helping others with Parkinson’s disease in the future.”